Search results for: protective clothing

Authors: Massimiliano Biagini, Marco Spinsanti, Gabriella De Angelis, Sara Tomei, Ilaria Ferlenghi, Maria Scarselli, Alessia Biolchi, Alessandro Muzzi, Brunella Brunelli, Silvana Savino, Marzia M. Giuliani, Isabel Delany, Paolo Costantino, Rino Rappuoli, Vega Masignani, Nathalie Norais

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The gram-negative bacterium Neisseria meningitidis serogroup B (MenB) is an exclusively human pathogen representing the major cause of meningitides and severe sepsis in infants and children but also in young adults. This pathogen is usually present in the 30% of healthy population that act as a reservoir, spreading it through saliva and respiratory fluids during coughing, sneezing, kissing. Among surface-exposed protein components of this diplococcus, factor H binding protein is a lipoprotein proved to be a protective antigen used as a component of the recently licensed Bexsero vaccine. fHbp is a highly variable meningococcal protein: to reflect its remarkable sequence variability, it has been classified in three variants (or two subfamilies), and with poor cross-protection among the different variants. Furthermore, the level of fHbp expression varies significantly among strains, and this has also been considered an important factor for predicting MenB strain susceptibility to anti-fHbp antisera. Different methods have been used to assess fHbp expression on meningococcal strains, however, all these methods use anti-fHbp antibodies, and for this reason, the results are affected by the different affinity that antibodies can have to different antigenic variants. To overcome the limitations of an antibody-based quantification, we developed a quantitative Mass Spectrometry (MS) approach. Selected Reaction Monitoring (SRM) recently emerged as a powerful MS tool for detecting and quantifying proteins in complex mixtures. SRM is based on the targeted detection of ProteoTypicPeptides (PTPs), which are unique signatures of a protein that can be easily detected and quantified by MS. This approach, proven to be highly sensitive, quantitatively accurate and highly reproducible, was used to quantify the absolute amount of fHbp antigen in total extracts derived from 105 clinical isolates, evenly distributed among the three main variant groups and selected to be representative of the fHbp circulating subvariants around the world. We extended the study at the genetic level investigating the correlation between the differential level of expression and polymorphisms present within the genes and their promoter sequences. The implications of fHbp expression on the susceptibility of the strain to killing by anti-fHbp antisera are also presented. To date this is the first comprehensive fHbp expression profiling in a large panel of Neisseria meningitidis clinical isolates driven by an antibody-independent MS-based methodology, opening the door to new applications in vaccine coverage prediction and reinforcing the molecular understanding of released vaccines.

Keywords: quantitative mass spectrometry, Neisseria meningitidis, vaccines, bexsero, molecular epidemiology

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Authors: Khelladi Hadj Mostefa, Krouf Djamil, Taleb-Dida Nawel

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Background: Obesity results from a prolonged imbalance between energy intake and energy expenditure, as depending on basal metabolic rate. Oils and proteins from sea have important therapeutic (such as obesity and hypercholesterolemia) and antioxidant effects. Sardine are a widely consumed fish in the Mediterranean region. Its consumption provides humans with various nutrients such as oils (rich in omega 3 plyunsaturated fatty acids)) and proteins. Methods: Sardine oil (SO) and sardine proteins (SP) were extracted and purified. Mixture of vegetable oils (olive-walnut-sunflower) were prepared from oils produced in Algeria. Eighteen wistar rats are fed a high fat diet enriched with 1% cholesterol for 30 days to induce obesity and hypercholesterolemia. The rats are divided into 3 groups. The first group consumes 20% sardine protein combined with 5% sardine oil (38% SFA (saturated fatty acids), 31% MIFA (monounsaturated fatty acids) and 31% PIFA (polyunsaturated fatty acids)) (SPso). The second group consumes 20% sardine protein combined with 5% of a mixture of vegetable oils (VO) containing 13% SFA, 58% MIFA and 29% PIFA (PSvo), and the third group consuming 20% casein combined with 5% of the mixture of vegetable oils and serves as a semi-synthetic reference (CASvo). Body weights and glycaemia are measured weekly After 28 days of experimentation, the rats are sacrificed, the blood and the liver removed. Serum assays of total cholesterol (TC) and triglycerides (TG) were performed by enzymatic colorimetric methods. Evaluation of lipid peroxidation was performed by assaying thiobarbituric acid reactive species (TBARS) and hydroperoxides values. The protein oxidation was performed by assaying carbonyl derivatives values. Finally, evaluation of antioxidant defense is made by measuring the activity of antioxidant enzymes, the superoxide dismutase (SOD) and the catalase (CAT).Results: After 28 days, the body weight (BW) of the rats increased significantly in SPso and SPvo groups compared to CAS group, by +11% and 7%, respectively. Cholesterolemia (TC) increased significantly in the SPso and SPvo groups compared to the CAS group (P<0.01), while triglyceridemia (TG) decreased significantly in the SPso group compared to SPvo and CAS groups (P<0.01). Albumin (marker of inflammation) increased in the PSs group compared to SPvo and CAS groups by +35% and +13%, respectively. The serum TBARS levels are -40% lower in SPso group compared to SPvo group, and they are -80% and -76% lower in SPso compared to SPvo and CAS groups, respectively. The level of carbonyls derivatives in the serum and liver are significantly reduced in the SPso group compared to the SPvo and CAS groups. Superoxide dismutase (SOD) activity decreased in liver of SPso group compared to SPvo group (P<0.01). While that of CAT is increased in liver tissue of SPso group compared to SPvo group (P<0.01). Conclusion: Sardine oil combined with sardine protein has a hypotriglyceridemic effect, reduces body weight, attenuates inflammation and seems to protect against lipid peroxidation and protein oxidation and increases antioxidant defense in hypercholesterolemic and obese rats. This could be in favor of a protective effect against obesity and cardiovascular diseases.

Keywords: rat, obesity, hypercholesterolemia, sardine protein, sardine oil, vegetable oils mixture, lipid peroxidation, protein oxidation, antioxidant defense

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Authors: Tzipi Eshet

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The primary objectives of this work are the examination of public preferences and attributed importance to different characteristics of coastal cliff protection alternatives, and drawing conclusions about the applicable alternative in Beit-Yanai beach. Erosion of coastal cliffs is a natural phenomenon that occurs in many places in the world. This creates problems along the coastlines, which are densely populated areas with highly developed economic activity. In recent years, various aspects of the aeolianite cliffs along the Israeli coast have been studied extensively. There is a consensus among researchers regarding a general trend of cliff retreat. This affects civilian infrastructure, wildlife habitats and heritage values, as well as Increases the risk to human life. The Israeli government, committed to the integrated coastal zones management approach, decided on a policy and guidelines to deal with cliff erosion, which includes establishing physical protection on land and in the sea, sand nourishment and runoff drainage. Physical protection solutions to reduce the rate of retreat of the cliffs are considerably important both for planning authorities and visitors to the beach. Direct costs of different protection alternatives, as well as external costs and benefits, may vary, thus affecting consumer preferences. Planning and execution of sustainable coastal cliff protection alternatives must take into account the different characteristics and their impact on aspects of economics, environment and leisure. The rocky shore of Beit-Yanai Beach was chosen as a case study to examine the nature of the influence of various protective solutions on consumer preferences. This beach is located in the center of Israel's coastline, and acts as a focus of attraction for recreation, land and sea sports, and educational activities as well. If no action will be taken, cliff retreat will continue. A survey was conducted to reveal the importance of coastal protection alternatives characteristics and the visual preferences to visitors at beach Beit-Yanai and residents living on the cliff (N=287). Preferences and willingness-to-pay were explored using Contingent-Ranking and Choice-Experiments techniques. Results show that visitors’ and residents’ willingness-to-pay for coastal cliff protection alternatives is affected both by financial and environmental aspects, as well as leisure. They prefer coastal cliff protection alternatives that are not visible and do not need constant maintenance, do not affect the quality of seawater or the habitats of wildlife and do not lower the security level of the swimmers. No significant difference was found comparing willingness-to-pay among local and non-local users. Additionally, they mostly prefer a protection solution which is integrated in the coastal landscape and maintains the natural appearance of the beach. Of the possible protection alternatives proposed for the protection of the cliff in Beit Yanai beach are two techniques that meet public preferences: rock revetments and submerged detached breakwaters. Results indicate that the visiting public prefer the implementation of these protection alternatives and will be willing to pay for them. Future actions to reduce retreat rate in Beit-Yanai have to consider implications on the economic, environmental and social conditions, along with weighting public interest against the interest of the individual.

Keywords: contingent-ranking, choice-experiments, coastal cliff protection, erosion of coastal cliffs, environment

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Authors: Hawraa Zbeeb, Hala Khalifeh, Mohamad Khalil, Francesca Storace, Francesca Baldini, Giulio Lupidi, Laura Vergani

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Sarcopoterium spinosum, a widely distributed spiny shrub belonging to the Rosaceae family, is rich in essential and beneficial constituents. In fact, S. spinosum fruits and roots are traditionally used as herbal medicine in the eastern Mediterranean landscape, and this shrub is mentioned as a medicinal plant in a large number of ethnobotanical surveys. Aqueous root extracts from S. spinosum are used by traditional medicinal practitioners for weight loss treatment of diabetes and pain. Moreover, the anti-diabetic activity of S. spinosum root extract has been reported in different studies, but the beneficial effects of aerial parts, especially fruits, have not been elucidated yet. The aim of the present study was to investigate the in vitro antioxidant and lipid-lowering properties of an ethanolic extract from S. spinosum fruits using both hepatic (FaO) and endothelial (HECV) cells in an attempt to evaluate its possible employment as a nutraceutical supplement. First of all, in vitro spectrophotometric assays were employed to characterize the extract. The total phenol content (TPC) was evaluated by Folin–Ciocalteu spectrophotometric method and the radical scavenging activity was tested by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. After that, the beneficial effects of the extract were tested on cells. FaO cells treated for 3 hours with 0.75 mM oleate/palmitate mix (1:2 molar ratio) mimic in vitro a moderate hepato-steatosis. HECV cells exposed for 1 hour to 100 µM H₂O₂ mimic an oxidative insult leading to oxidative stress conditions. After the metabolic and oxidative insult, both cell lines were treated with increasing concentrations of the S. spinosum extract (1, 10, 25 µg/mL) for 24 hours. The results showed the S. spinosum ethanolic extract is rather rich in phenols (TPC of 18.6 mgGAE/g dry extracts). Moreover, the extract showed a good scavenging ability in vitro (IC₅₀ 15.9 µg/ml and 10.9 µg/ml measured by DPPH and ABTS assays, respectively). When the extract was tested on cells, the results showed that it could ameliorate some markers of cell dysfunction. The three concentrations of the extract led to a significant decrease in the intracellular triglyceride (TG) content in steatotic FaO cells measured by spectrophotometric assay. On the other hand, HECV cells treated with increasing concentrations of the extract did not result in a significant decrease in both lipid peroxidation measured by the Thiobarbituric Acid Reactive Substances (TBARS) assay, and in reactive oxygen species (ROS) production measured by fluorometric analysis after DCF staining. Interestingly, the ethanolic extract was able to accelerate the wound repair of confluent HECV cells with respect to H₂O₂-insulted cells as measured by T-scratch assay. Taken together, these results seem to indicate that the ethanol extract from S. spinosum fruits is rich in phenol compounds and plays considerable lipid-lowering activity in vitro on steatotic hepatocytes and accelerates wound healing repair on endothelial cells. In light of that, the ethanolic extract from S. spinosum fruits could be a potential candidate for nutraceutical applications.

Keywords: antioxidant activity, ethanolic extract, lipid-lowering activity, phenolic compounds, Sarcopoterium spinosum fruits

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Authors: Paul Flynn, Luke O’Donnell

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There is a pressing societal need for educators in formal and non-formal settings to develop pedagogical frameworks, programmes, and interventions that support the development of transversal skills for life beyond the classroom. These skills include communication, collaboration, interpersonal relationship building, problem-solving, and planning, and organizational skills; or lifeworld literacies encountered first hand. This is particularly true for young people aged between 15-18. This demographic represents both the future of society and those best positioned to take advantage of well-designed, structured educational supports within and across formal and non-formal settings. Secondary school history has been identified as an appropriate area of study which deftly develops many of those transversal skills so crucial to positive societal engagement. However, in the formal context, students often challenge history’s relevance to their own lived experience and dismiss it as a study option. In response to such challenges, teachers will often design stimulating lessons which are often well-received. That said, some students continue to question modern-day connections, presenting a persistent and pervasive classroom distraction. The continuing decline in numbers opting to study second-level history indicates an erosion of what should be a critical opportunity to develop all-important lifeworld literacies within formal education. In contrast, students readily acknowledge relevance in non-formal settings where many participants meaningfully engage with history by way of student-focused activities. Furthermore, many do so without predesigned pedagogical aids which support transversal skills development as embodied learning outcomes. As this paper will present, there is a dearth of work pertaining to the circular subject of history and its embodied learning outcomes, including lifeworld literacies, in formal and non-formal settings. While frequently challenging to reconcile formal (often defined by strict curricula and examination processes), and non-formal engagement with history, opportunities do exist. In the Irish context, this is exemplified by a popular university outreach programme: breaking the SEAL. This programme supports second-level history students as they fulfill curriculum requirements in completing a research study report. This report is a student-led research project pulling on communication skills, collaboration with peers and teachers, interpersonal relationships, problem-solving, and planning and organizational skills. Completion of this process has been widely recognized as excellent preparation not only for higher education (third level) but work-life demands as well. Within a formal education setting, the RSR harnesses non-formal learning virtues and exposes students to limited aspects of independent learning that relate to a professional work setting –a lifeworld literacy. Breaking the SEAL provides opportunities for students to enhance their lifeworld literacy by engaging in an independent research and learning process within the protective security of the classroom and its teacher. This paper will highlight the critical role this programme plays in preparing participating students (n=315) for life after compulsory education and presents examples of how lifeworld literacies may be developed through a scaffolded process of historical research and reporting anchored in non-formal contexts.

Keywords: history, education, literacy, transversal skills

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Authors: Vidhya Venugopal, Jeremiah Chinnadurai, Rebekah A. I. Lucas, Tord Kjellstrom, Bruno Lemke

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Introduction: The effects of climate change (CC) are largely discussed across the globe in terms of impacts on the environment and the general population, but the impacts on workers remain largely unexplored. The predicted rise in temperatures and heat events in the CC scenario have health implications on millions of workers in physically exerting jobs. The current health and productivity risks associated with heat exposures are characterized, future risk estimates as temperature rises and recommendations towards developing protective and preventive occupational health and safety guidelines for India are discussed. Methodology: Cross-sectional studies were conducted in several occupational sectors with workers engaged in moderate to heavy labor (n=1580). Quantitative data on heat exposures (WBGT°C), physiological heat strain indicators viz., Core temperature (CBT), Urine specific gravity (USG), Sweat rate (SwR) and qualitative data on heat-related health symptoms and productivity losses were collected. Data were analyzed for associations between heat exposures, health and productivity outcomes related to heat stress. Findings: Heat conditions exceeded the Threshold Limit Value (TLV) for safe manual work in 66% of the workers across several sectors (Avg.WBGT of 28.7°C±3.1°C). Widespread concerns about heat-related health outcomes (86%) were prevalent among workers exposed to high TLVs, with excessive sweating, fatigue and tiredness being commonly reported by workers. The heat stress indicators, core temperature (14%), Sweat rate (8%) and USG (9%), were above normal levels in the study population. A significant association was found between rise in Core Temperatures and WBGT exposures (p=0.000179) Elevated USG and SwR in the worker population indicate moderate dehydration, with potential risks of developing heat-related illnesses. In a steel industry with high heat exposures, an alarming 9% prevalence of kidney/urogenital anomalies was observed in a young workforce. Heat exposures above TLVs were associated with significantly increased odds of various adverse health outcomes (OR=2.43, 95% CI 1.88 to 3.13, p-value = <0.0001) and productivity losses (OR=1.79, 95% CI 1.32 to 2.4, p-value = 0.0002). Rough estimates for the number of workers who would be subjected to higher than TLV levels in the various RCP scenarios are RCP2.6 =79%, RCP4.5 & RCP6 = 81% and at RCP 8.5 = 85%. Rising temperatures due to CC has the capacity to further reduce already compromised health and productivity by subjecting the workers to increased heat exposures in the RCP scenarios are of concern for the country’s occupational health and economy. Conclusion: The findings of this study clearly identify that health protection from hot weather will become increasingly necessary in the Indian subcontinent and understanding the various adaptation techniques needs urgent attention. Further research with a multi-targeted approach to develop strategies for implementing interventions to protect the millions of workers is imperative. Approaches to include health aspects of climate change within sectoral and climate change specific policies should be encouraged, via a number of mechanisms, such as the “Health in All Policies” approach to avert adverse health and productivity consequences as climate change proceeds.

Keywords: heat stress, occupational health, productivity loss, heat strain, adverse health outcomes

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Authors: Shana Malio-Satele, Lemalu Silao Vaisola Sefo

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Introductory Statement: South Seas Healthcare is Ōtara’s largest Pacific health provider in South Auckland, New Zealand. Our vision is excellent health and well-being for Pacific people and all communities through strong Pacific values. During the DELTA and Omicron outbreak of COVID-19, our Pacific people, indigenous Māori, and the community of South Auckland were disproportionately affected and faced significant hardship with existing inequities magnified. This study highlights the community-based learnings of harnessing community-based strengths such as indigenous resilience, family-informed experiences and stories that provide critical insights that inform health reform changes that will be sustainable and equitable for all indigenous populations. This study is based on critical learnings acquired during COVID-19 that challenge the deficit narrative common in healthcare about indigenous populations. This study shares case studies of marginalised groups and religious groups and the successful application of indigenous cultural strengths, such as collectivism, positive protective factors, and using trusted relationships to create meaningful change in the way healthcare is delivered. The significance of this study highlights the critical conditions needed to adopt a community-informed way of creating integrated healthcare that works and the role that the community can play in being part of the solution. Methodologies: Key methodologies utilised are indigenous and Pacific-informed. To achieve critical learnings from the community, Pacific research methodologies, heavily informed by the Polynesian practice, were applied. Specifically, this includes; Teu Le Va (Understanding the importance of trusted relationships as a way of creating positive health solutions); The Fonofale Methodology (A way of understanding how health incorporates culture, family, the physical, spiritual, mental and other dimensions of health, as well as time, context and environment; The Fonua Methodology – Understanding the overall wellbeing and health of communities, families and individuals and their holistic needs and environmental factors and the Talanoa methodology (Researching through conversation, where understanding the individual and community is through understanding their history and future through stories). Major Findings: Key findings in the study included: 1. The collectivist approach in the community is a strengths-based response specific to populations, which highlights the importance of trusted relationships and cultural values to achieve meaningful outcomes. 2. The development of a “village model” which identified critical components to achieving health reform change; system navigation, a sense of service that was culturally responsive, critical leadership roles, culturally appropriate support, and the ability to influence the system enablers to support an alternative way of working. Concluding Statement: There is a strong connection between community-based strengths being implemented into healthcare strategies and reforms and the sustainable success of indigenous populations and marginalised communities accessing services that are cohesive, equitably resourced, accessible and meaningful for families. This study highlights the successful community-informed approaches and practices used during the COVID-19 response in New Zealand that are now being implemented in the current health reform.

Keywords: indigenous voice, community voice, health reform, New Zealand

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Authors: Zuzana Tatarkova, Ivana Pilchova, Michal Cibulka, Martin Kolisek, Peter Racay, Peter Kaplan

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Introduction: Normal functioning of mitochondria is crucial for cardiac performance. Mitochondria undergo mitophagy and biogenesis, and mitochondrial proteins are subject to extensive post-translational modifications. The state of mitochondrial homeostasis reflects overall cellular fitness and longevity. Perturbed mitochondria produce less ATP, release greater amounts of reactive molecules, and are more prone to apoptosis. Therefore mitochondrial turnover is an integral aspect of quality control in which dysfunctional mitochondria are selectively eliminated through mitophagy. Currently, the progressive deterioration of physiological functions is seen as accumulation of modified/damaged proteins with limiting regenerative ability and disturbance of such affected protein-protein communication throughout aging in myocardial cells. Methodologies: For our study was used immunohistochemistry, biochemical methods: spectrophotometry, western blotting, immunodetection as well as more sophisticated 2D electrophoresis and mass spectrometry for evaluation protein-protein interactions and specific post-translational modification. Results and Discussion: Mitochondrial stress response to reactive species was evaluated as electron transport chain (ETC) complexes, redox-active molecules, and their possible communication. Protein-protein interactions revealed a strong linkage between age and ETC protein subunits. Redox state was strongly affected in senescent mitochondria with shift in favor of more pro-oxidizing condition within cardiomyocytes. Acute myocardial ischemia and ischemia-reperfusion (IR) injury affected ETC complexes I, II and IV with no change in complex III. Ischemia induced decrease in total antioxidant capacity, MnSOD, GSH and catalase activity with recovery in some extent during reperfusion. While MnSOD protein content was higher in IR group, activity returned to 95% of control. Nitric oxide is one of the biological molecules that can out compete MnSOD for superoxide and produce peroxynitrite. This process is faster than dismutation and led to the 10-fold higher production of nitrotyrosine after IR injury in adult with higher protection in senescent ones. 2D protein profiling revealed 140 mitochondrial proteins, 12 of them with significant changes after IR injury and 36 individual nitrotyrosine-modified proteins further identified by mass spectrometry. Linking these two groups, 5 proteins were altered after IR as well as nitrated, but only one showed massive nitration per lowering content of protein after IR injury in adult. Conclusions: Senescent cells have greater proportion of protein content, which might be modulated by several post-translational modifications. If these protein modifications are connected to functional consequences and protein-protein interactions are revealed, link may lead to the solution. Assume all together, dysfunctional proteostasis can play a causative role and restoration of protein homeostasis machinery is protective against aging and possibly age-related disorders. This work was supported by the project VEGA 1/0018/18 and by project 'Competence Center for Research and Development in the field of Diagnostics and Therapy of Oncological diseases', ITMS: 26220220153, co-financed from EU sources.

Keywords: aging heart, mitochondria, proteomics, redox state

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Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

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Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

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Authors: Jyh-Ping Chen, Yu-Tin Lai

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Wound healing is a complicated process involving overlapping hemostasis, inflammation, proliferation, and maturation phases. Ideal wound dressings can replace native skin functions in full thickness skin wounds through faster healing rate and also by reducing scar formation. Poly(lactic-co-glycolic acid) (PLGA) is an U.S. FDA approved biodegradable polymer to be used as ideal wound dressing material. Several in vitro and in vivo studies have demonstrated the effectiveness of curcumin in decreasing the release of inflammatory cytokines, inhibiting enzymes associated with inflammations, and scavenging free radicals that are the major cause of inflammation during wound healing. Heparin has binding affinities to various growth factors. With the unique and beneficial features offered by those molecules toward the complex process of wound healing, we postulate a composite wound dressing constructed from PLGA, curcumin and heparin would be a good candidate to accelerate scarless wound healing. In this work, we use electrospinning to prepare curcumin-loaded aligned PLGA nanofibrous membranes (PC NFMs). PC NFMs were further subject to oxygen plasma modification and surfaced-grafted with heparin through carbodiimide-mediated covalent bond formation to prepare curcumin-loaded PLGA-g-heparin (PCH) NFMs. The nanofibrous membranes could act as three-dimensional scaffolds to attract fibroblast migration, reduce inflammation, and increase wound-healing related growth factors concentrations at wound sites. From scanning electron microscopy analysis, the nanofibers in each NFM are with diameters ranging from 456 to 479 nm and with alignment angles within  0.5°. The NFMs show high tensile strength and good water absorptivity and provide suitable pore size for nutrients/wastes transport. Exposure of human dermal fibroblasts to the extraction medium of PC or PCH NFM showed significant protective effects against hydrogen peroxide than PLGA NFM. In vitro wound healing assays also showed that the extraction medium of PCH NFM showed significantly better migration ability toward fibroblasts than PC NFM, which is further better than PLGA NFM. The in vivo healing efficiency of the NFMs was further evaluated by a full thickness excisional wound healing diabetic rat model. After 14 days, PCH NFMs exhibits 86% wound closure rate, which is significantly different from other groups (79% for PC and 73% for PLGA NFM). Real-time PCR analysis indicated PC and PCH NFMs down regulated anti-oxidative enzymes like glutathione peroxidase (GPx) and superoxide dismutase (SOD), which are well-known transcription factors involved in cellular inflammatory responses to stimuli. From histology, the wound area treated with PCH NFMs showed more vascular lumen formation from immunohistochemistry of α-smooth muscle actin. The wound site also had more collagen type III (65.8%) expression and less collagen type I (3.5%) expression, indicating scar-less wound healing. From Western blot analysis, the PCH NFM showed good affinity toward growth factors from increased concentration of transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2) at the wound site to accelerate wound healing. From the results, we suggest PCH NFM as a promising candidate for wound dressing applications.

Keywords: Curcumin, heparin, nanofibrous membrane, poly(lactic-co-glycolic acid) (PLGA), wound dressing

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Authors: Dirk Bruland, Paulo Pinheiro, Ullrich Bauer

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Introduction: Over 3 million children, about one quarter of all students, experience at least one parent with mental disorder in Germany every year. Children of mentally-ill parents are at considerably higher risk of developing serious mental health problems. The different burden patterns and coping attempts often become manifest in children's school lives. In this context, schools can have an important protective function, but can also create risk potentials. In reference to Jorm, pupil-related teachers’ mental health literacy (Teacher-MHL) includes the ability to recognize change behaviour, the knowledge of risk factors, the implementation of first aid intervention, and seeking professional help (teacher as gatekeeper). Although teachers’ knowledge and increased awareness of this topic is essential, the literature provides little information on the extent of teachers' abilities. As part of a German-wide research consortium on health literacy, this project, launched in March for 3 years, will conduct evidence-based mental health literacy research. The primary objective is to measure Teacher-MHL in the context of pupil-related psychosocial factors at primary and secondary schools (grades 5 & 6), while also focussing on children’s social living conditions. Methods: (1) A systematic literature review in different databases to identify papers with regard to Teacher-MHL (completed). (2) Based on these results, an interview guide was developed. This research step includes a qualitative pre-study to inductively survey the general profiles of teachers (n=24). The evaluation will be presented on the conference. (3) These findings will be translated into a quantitative teacher survey (n=2500) in order to assess the extent of socio-analytical skills of teachers as well as in relation to institutional and individual characteristics. (4) Based on results 1 – 3, developing a training program for teachers. Results: The review highlights a lack of information for Teacher-MHL and their skills, especially related to high-risk-groups like children of mentally ill parents. The literature is limited to a few studies only. According to these, teacher are not good at identifying burdened children and if they identify those children they do not know how to handle the situations in school. They are not sufficiently trained to deal with these children, especially there are great uncertainties in dealing with the teaching situation. Institutional means and resources are missing as well. Such a mismatch can result in insufficient support and use of opportunities for children at risk. First impressions from the interviews confirm these results and allow a greater insight in the everyday school-life according to critical life events in families. Conclusions: For the first time schools will be addressed as a setting where children are especially "accessible" for measures of health promotion. Addressing Teacher-MHL gives reason to expect high effectiveness. Targeting professionals' abilities for dealing with this high-risk-group leads to a discharge for teacher themselves to handle those situations and increases school health promotion. In view of the fact that only 10-30% of such high-risk families accept offers of therapy and assistance, this will be the first primary preventive and health-promoting approach to protect the health of a yet unaffected, but particularly burdened, high-risk group.

Keywords: children of mentally ill parents, health promotion, mental health literacy, school

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Authors: Azza A. Ali, Toqa M. Elnahhas, Abeer I. Abd El-Fattah, Mona M. Kamal, Karema Abu-Elfotuh

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Background: Environmental pollution with the different aluminium (Al) containing compounds especially those in industrial waste water exposes people to higher than normal levels of Al that represents an environmental risk factor. Cosmetics, Al ware, and containers are also sources of Al besides some foods and food additives. In addition to its known neurotoxicity, Al affects other body structures like skeletal system, blood cells, liver and kidney. Accumulation of Al in kidney and liver induces nephrotoxicity and hepatotoxicity. Coenzyme Q10 (CoQ10) is a pseudo-vitamin substance primarily present in the mitochondria. It is a powerful antioxidant and acts as radical scavenger. Wheat grass is a natural product that contains carbohydrates, proteins, vitamins, minerals, enzymes and has antioxidant, anti-inflammatory, anticancer and cardiovascular protection activities. Cocoa is an excellent source of iron, potent antioxidants and can protect against many diseases. Vinpocetine is an antioxidant and anti inflammatory while zinc is an essential trace element involved in cell division and its deficiency is observed in many types of liver disease. Objective: To evaluate and compare the potency of different drugs (CoQ10, wheatgrass, cocoa, vinpocetine and zinc) against nephro- and hepato-toxicity induced by Al in rats. Methods: Rats were divided to seven groups and received daily for three weeks either saline for control group or AlCl3 (70 mg/kg, IP) for Al-toxicity model groups. Five groups of Al-toxicity model (treated groups) were orally received together with Al each of the following; CoQ10 (200mg/kg), wheat grass (100mg/kg), cocoa powder (24mg/kg), vinpocetine (20mg/kg) or zinc (32mg/kg). Biochemical changes in the serum level of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) as well as total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea were measured. Liver and kidney specimens from all groups were also collected for the assessment of hepatic and nephrotic level of inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3, oxidative parameters (MDA, SOD, TAC, NO) and DNA fragmentation. Histopathological changes in liver and kidney were also evaluated. Results: Three weeks of AlCl3 (70 mg/kg, IP) exposure induced nephro- and hepato-toxicity in rats. Treatment by the all used drugs showed protection against hazards of AlCl3. The protective effects were indicated by the significant decrease in ALT, AST, ALP, LDH as well as total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels which were increased by Al. Liver and kidney of the treated groups showed decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation which were increased by Al, together with significant increase in total proteins, SOD and TAC which were decreased by Al. The protection against both nephro- and hepato-toxicity was more pronounced especially with CoQ10 and wheat grass than the other used drugs. Histopathological examinations confirmed the biochemical results of toxicity and of protection. Conclusion: Protection from nephrotoxicity, hepatotoxicity and the consequent degenerations induced by Al can be achieved by using different drugs as CoQ10, wheatgrass, cocoa, vinpocetine and zinc, but CoQ10 as well as wheat grass possesses the most superior protection.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, coenzyme Q10, wheatgrass, cocoa, vinpocetine, zinc

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Authors: Layla Haidar, Shari Esquenazi-Karonika

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Introduction: Mental health includes one’s emotional, psychological, and interpersonal well-being; it ranges from “good” to “poor” on a continuum. At the individual-level, it affects how a person thinks, feels, and acts. Moreover, it determines how they cope with stress, relate to others, and interface with their surroundings. Research has yielded that mental health is directly related with short- and long-term physical health (including chronic disease), health risk behaviors, education-level, employment, and social relationships. As is the case with physical conditions like diabetes, heart disease, and cancer, mitigating the behavioral and genetic risks of debilitating mental health conditions like anxiety and depression can nurture a healthier quality of mental health throughout one’s life. In order to maximize the benefits of prevention, it is important to identify modifiable risks and develop protective habits earlier in life. Methods: The Adolescent Behaviors and Experiences Survey (ABES) dataset was used for this study. The ABES survey was administered to high school students (9th-12th grade) during January 2021- June 2021 by the Centers for Disease Control and Prevention (CDC). The data was analyzed to identify any associations between feelings of sadness, hopelessness, or increased suicidality among high school students with relation to their participation on one or more sports teams and their average daily consumed screen time. Data was analyzed using descriptive and multivariable analytic techniques. A multinomial logistic regression of each variable was conducted to examine if there was an association, while controlling for grade-level, sex, and race. Results: The findings from this study are insightful for administrators and policymakers who wish to address mounting concerns related to student mental health. The study revealed that compared to a student who participated on zero sports teams, students who participated in 1 or more sports teams showed a significantly increased risk of depression (p<0.05). Conversely, the rate of depression in students was significantly less in those who consumed 5 or more hours of screen time per day, compared to those who consumed less than 1 hour per day of screen time (p<0.05). Conclusion: These findings are informative and highlight the importance of understanding the nuances of student participation on sports teams (e.g., physical exertion, social dynamics of team, and the level of competitiveness within the sport). Likewise, the context of an individual’s screen time (e.g., social media, engaging in team-based video games, or watching television) can inform parental or school-based policies about screen time activity. Although physical activity has been proven to be important for emotional and physical well-being of youth, playing on multiple teams could have negative consequences on the emotional state of high school students potentially due to fatigue, overtraining, and injuries. Existing literature has highlighted the negative effects of screen time; however, further research needs to consider the type of screen-based consumption to better understand its effects on mental health.

Keywords: behavioral science, mental health, adolescents, prevention

Procedia PDF Downloads 72

Authors: Chenyi Ma

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Background: The second costliest hurricane in U.S. history, Sandy landed in southern New Jersey on October 29, 2012, and struck the entire state with high winds and torrential rains. The disaster killed more than 100 people, left more than 8.5 million households without power, and damaged or destroyed more than 200,000 homes across the state. Immediately after the disaster, public policy support was provided in nine coastal counties that constituted 98% of the major and severely damaged housing units in NJ overall. The programs include Individuals and Households Assistance Program, Small Business Loan Program, National Flood Insurance Program, and the Federal Emergency Management Administration (FEMA) Public Assistance Grant Program. In the most severely affected counties, additional funding was provided through Community Development Block Grant: Reconstruction, Rehabilitation, Elevation, and Mitigation Program, and Homeowner Resettlement Program. How these policies individually and as a whole impacted housing recovery across communities with different socioeconomic and demographic profiles has not yet been studied, particularly in relation to damage levels. The concept of community social vulnerability has been widely used to explain many aspects of natural disasters. Nevertheless, how communities are vulnerable has been less fully examined. Community resilience has been conceptualized as a protective factor against negative impacts from disasters, however, how community resilience buffers the effects of vulnerability is not yet known. Because housing recovery is a dynamic social and economic process that varies according to context, this study examined the path from community vulnerability and resilience to housing recovery looking at both community characteristics and policy interventions. Sample/Methods: This retrospective longitudinal case study compared a literature-identified set of pre-disaster community characteristics, the effects of multiple public policy programs, and a set of time-variant community resilience indicators to changes in housing stock (operationally defined by percent of building permits to total occupied housing units/households) between 2010 and 2014, two years before and after Hurricane Sandy. The sample consisted of 51 municipalities in the nine counties in which between 4% and 58% of housing units suffered either major or severe damage. Structural equation modeling (SEM) was used to determine the path from vulnerability to the housing recovery, via multiple public programs, separately and as a whole, and via the community resilience indicators. The spatial analytical tool ArcGIS 10.2 was used to show the spatial relations between housing recovery patterns and community vulnerability and resilience. Findings: Holding damage levels constant, communities with higher proportions of Hispanic households had significantly lower levels of housing recovery while communities with households with an adult >age 65 had significantly higher levels of the housing recovery. The contrast was partly due to the different levels of total public support the two types of the community received. Further, while the public policy programs individually mediated the negative associations between African American and female-headed households and housing recovery, communities with larger proportions of African American, female-headed and Hispanic households were “vulnerable” to lower levels of housing recovery because they lacked sufficient public program support. Even so, higher employment rates and incomes buffered vulnerability to lower housing recovery. Because housing is the "wobbly pillar" of the welfare state, the housing needs of these particular groups should be more fully addressed by disaster policy.

Keywords: community social vulnerability, community resilience, hurricane, public policy

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Authors: Nicki Mohammadi, Emma Reford, Natalia Romano Spica, Laura Tabacof, Jenna Tosto-Mancuso, David Putrino, Christopher P. Kellner

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Introductory Statement: The onset of the COVID-19 pandemic demanded an unprecedented need for the rapid development, dispersal, and application of infection testing. However, despite the impressive mobilization of resources, individuals were incredibly limited in their access to tests, particularly during the initial months of the pandemic (March-April 2020) in New York City (NYC). Access to COVID-19 testing is crucial in understanding patients’ illness experiences and integral to the development of COVID-19 standard-of-care protocols, especially in the context of overall access to healthcare resources. Succinct Description of basic methodologies: 18 Patients in a COVID-19 Remote Patient Monitoring Program (Precision Recovery within the Mount Sinai Health System) were interviewed regarding their experience with COVID-19 during the first wave (March-May 2020) of the COVID-19 pandemic in New York City. Patients were asked about their experiences navigating COVID-19 diagnoses, the health care system, and their recovery process. Transcribed interviews were analyzed for thematic codes, using grounded theory to guide the identification of emergent themes and codebook development through an iterative process. Data coding was performed using NVivo12. References for the domain “testing” were then extracted and analyzed for themes and statistical patterns. Clear Indication of Major Findings of the study: 100% of participants (18/18) referenced COVID-19 testing in their interviews, with a total of 79 references across the 18 transcripts (average: 4.4 references/interview; 2.7% interview coverage). 89% of participants (16/18) discussed the difficulty of access to testing, including denial of testing without high severity of symptoms, geographical distance to the testing site, and lack of testing resources at healthcare centers. Participants shared varying perspectives on how the lack of certainty regarding their COVID-19 status affected their course of recovery. One participant shared that because she never tested positive she was shielded from her anxiety and fear, given the death toll in NYC. Another group of participants shared that not having a concrete status to share with family, friends and professionals affected how seriously onlookers took their symptoms. Furthermore, the absence of a positive test barred some individuals from access to treatment programs and employment support. Concluding Statement: Lack of access to COVID-19 testing in the first wave of the pandemic in NYC was a prominent element of patients’ illness experience, particularly during their recovery phase. While for some the lack of concrete results was protective, most emphasized the invalidating effect this had on the perception of illness for both self and others. COVID-19 testing is now widely accessible; however, those who are unable to demonstrate a positive test result but who are still presumed to have had COVID-19 in the first wave must continue to adapt to and live with the effects of this gap in knowledge and care on their recovery. Future efforts are required to ensure that patients do not face barriers to care due to the lack of testing and are reassured regarding their access to healthcare. Affiliations- 1Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY 2Abilities Research Center, Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY

Keywords: accessibility, COVID-19, recovery, testing

Procedia PDF Downloads 158

Authors: Ronahlee Asuncion

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The nature of their work and employment relationship make domestic workers easy prey to abuse, maltreatment, and exploitation. Considering their plight, this research was conceptualized and examined the: a) level of awareness of Filipino domestic workers on occupational safety and health (OSH); b) their issues/problems/concerns on OSH; c) their intervention strategies at work to address OSH related issues/problems/concerns; d) issues/problems/concerns of government, employers, and non-government organizations with regard to implementation of OSH to Filipino domestic workers; e) the role of government, employers and non-government organizations to help Filipino domestic workers address OSH related issues/problems/concerns; and f) the necessary policy amendments/initiatives/programs to address OSH related issues/problems/concerns of Filipino domestic workers. The study conducted a survey using non-probability sampling, two focus group discussions, two group interviews, and fourteen face-to-face interviews. These were further supplemented with an email correspondence to a key informant based in another country. Books, journals, magazines, and relevant websites further substantiated and enriched data of the research. Findings of the study point to the fact that domestic workers have low level of awareness on OSH because of poor information drive, fragmented implementation of the Domestic Workers Act, inactive campaign at the barangay level, weakened advocacy for domestic workers, absence of law on OSH for domestic workers, and generally low safety culture in the country among others. Filipino domestic workers suffer from insufficient rest, long hours of work, heavy workload, occupational stress, poor accommodation, insufficient hours of sleep, deprivation of day off, accidents and injuries such as cuts, burns, slipping, stumbling, electrical grounding, and fire, verbal, physical and sexual abuses, lack of medical assistance, none provision of personal protective equipment (PPE), absence of knowledge on the proper way of lifting, working at heights, and insufficient food provision. They also suffer from psychological problems because of separation from one’s family, limited mobility in the household where they work, injuries and accidents from using advanced home appliances and taking care of pets, low self-esteem, ergonomic problems, the need to adjust to all household members who have various needs and demands, inability to voice their complaints, drudgery of work, and emotional stress. With regard to illness or health problems, they commonly experience leg pains, back pains, and headaches. In the absence of intervention programs like those offered in the formal employment set up, domestic workers resort to praying, turn to family, relatives and friends for social and emotional support, connect with them through social media like Facebook which also serve as a means of entertainment to them, talk to their employer, and just try to be optimistic about their situation. Promoting OSH for domestic workers is very challenging and complicated because of interrelated factors such as cultural, knowledge, attitudinal, relational, social, resource, economic, political, institutional and legal problems. This complexity necessitates using a holistic and integrated approach as this is not a problem requiring simple solutions. With this recognition comes the full understanding that its success involves the action and cooperation of all duty bearers in attaining decent work for domestic workers.

Keywords: decent work, Filipino domestic workers, occupational safety and health, working conditions

Procedia PDF Downloads 225

Authors: Wafaa Hasan

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In May of 2022, Palestinian parents in Toronto, Canada, became aware that educators and staff in the Toronto District School Board were attempting to include the International Holocaust and Remembrance Definition of Antisemitism (IHRA) in The Child Abuse and Neglect Policy of the largest school board in Canada, The Toronto District School Board (TDSB). The idea was that if students were to express any form of antisemitism, as defined by the IHRA, then an investigation could follow with Child Protective Services (CPS). That is, the student’s parents could be reported to the state and investigated for custodial rights to their children. The TDSB has set apparent goals for “Decolonizing Pedagogy” (“TDSB Equity Leadership Competencies”), Culturally Responsive and Relevant Practices (CRRP) and inclusive education. These goals promote the centering of colonized, racialized and marginalized voices. CRRP cannot be effective without the application of anti-racist and settler colonial analyses. In order for CRRP to be effective, school boards need a comprehensive understanding of the ways in which the vilification of Palestinians operates through anti-indigenous and white supremacist systems and logic. Otherwise, their inclusion will always be in tension with the inclusion of settler colonial agendas and worldviews. Feminist maternalism frames racial mothering as degenerate (viewing the contributions of racialized students and their parents as products of primitive and violent cultures) and also indirectly inhibits the actualization of the tenets of CRRP and inclusive education through its extensions into the welfare state and public education. The contradiction between the tenets of CRRP and settler colonial systems of erasure and repression is resolved by the continuation of tactics to 1) force assimilation, 2) punish those who push back on that assimilation and 3) literally fragment familial and community structures of racialized students, educators and parents. This paper draws on interdisciplinary (history, philosophy, anthropology) critiques of white feminist “maternalism” from the 19th century onwards in North America and Europe (Jacobs, Weber), as well as “anti-racist education” theory (Dei), and more specifically,” culturally responsive learning,” (Muhammad) and “bandwidth” pedagogy theory (Verschelden) to make its claims. This research contributes to vibrant debates about anti-racist and decolonial pedagogies in public education systems globally. This paper also documents first-hand interviews and experiences of diasporic Palestinian mothers and motherhoods and situates their experiences within longstanding histories of white feminist maternalist (and eugenicist) politics. This informal qualitative data from "participatory conversations" (Swain) is situated within a set of formal interview data collected with Palestinian women in the West Bank (approved by the McMaster University Humanities Research Ethics Board) relating to white feminist maternalism in the peace and dialogue industry.

Keywords: decolonial feminism, maternal feminism, anti-racist pedagogies, settler colonial studies, motherhood studies, pedagogy theory, cultural theory

Procedia PDF Downloads 37

Authors: Kristina Karapetyan, Flora Tkhruni, Tsovinar Balabekyan, Arevik Israyelyan, Tatyana Khachatryan

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The ability of the lactic acid bacteria (LAB) to prevent and cure a variety of diseases, their protective role against infections and colonization of pathogenic microorganisms in the digestive tract, has lead to the coining of the term probiotics or pro-life. LAB inhibiting the growth of pathogenic and food spoilage microorganisms, maintaining the nutritive quality and improving the shelf life of foods. They have also been used as flavor and texture producers. Enterococcus strains have been used for treatment of diseases such as diarrhea or antibiotic associated diarrhea, inflammatory pathologies that affect colon such as irritable bowel syndrome, or immune regulation, diarrhea caused by antibiotic treatments. The obtaining and investigation of biological properties of proteinoceous antibiotics, on the basis of probiotic LAB shown, that bacteriocins, metabiotics, and peptides of LAB represent bactericides have a broad range of activity and are excellent candidates for development of new prophylactic and therapeutic substances to complement or replace conventional antibiotics. The genotyping by 16S rRNA sequencing for LAB were used. Cell free culture broth (CFC) broth was purified by the Gel filtration method on the Sephadex Superfine G 25 resin. Antimicrobial activity was determined by spot-on-lawn method and expressed in arbitrary units (AU/ml). The diversity of multidrug-resistance (MDR) of pathogenic strains to antibiotics, most widely used for treatment of human diseases in the Republics of Armenia and Nagorno Karabakh were examined. It was shown, that difference of resistance of pathogens to antibiotics depends on their isolation sources. The influences of partially purified antimicrobial preparations (AMP), obtained from the different strains of Enterococcus genus on the growth of MDR pathogenic bacteria were investigated. It was shown, that bacteriocin containing partially purified preparations, obtained from different strains of Enterococcus faecium and durans species, possess bactericidal or bacteriostatic activity against antibiotic resistant intestinal, spoilage and food-borne pathogens such as Listeria monocytogenes, Staphylococcus aureus, E. coli, and Salmonella. Endemic strains of LAB, isolated from Matsoni made from donkey, buffalo and goat milk, shown broad spectrum of activity against food spoiling microorganisms, moulds and fungi, such as Salmonella sp., Esherichia coli, Aspergillus and Penicillium species. Highest activity against MDR pathogens shown bacteria, isolated from goat milk products. High stability of the investigated strains of the genus Enerococcus, isolated from samples of matsun from different regions of Nagorno-Karabakh (NKR) to the antibiotics was shown. The obtained data show high stability of the investigated different strains of the genus Enerococcus. The high genetic diversity in Enterococcus group suggests adaptations for specific mutations in different environments. Thus, endemic strains of LAB are able to produce bacteriocins with high and different inhibitory activity against broad spectrum of microorganisms isolated from different sources and belong to different taxonomic group. Prospect of the use of certain antimicrobial preparations against pathogenic strains is obvious. These AMP can be applied for long term use against different etiology antibiotic resistant pathogens for prevention or treatment of infectional diseases as an alternative to antibiotics.

Keywords: antimicrobial biopreparation, endemic lactic acid bacteria, intra-species diversity, multidrug resistance of pathogens

Procedia PDF Downloads 285

Authors: Haji Mohammad Zulfan Farhi Bin Haji Sulaini, Mohammad Azeezudde’en Bin Mohd Ismaon

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The demands placed on military athletes extend beyond physical prowess to encompass cognitive resilience in high-stress environments. This study investigates the effects of resilience training on the cognitive performance of military athletes, shedding light on the potential benefits and implications for optimizing their overall readiness. In a rapidly evolving global landscape, armed forces worldwide are recognizing the importance of cognitive resilience alongside physical fitness. The study employs a mixed-methods approach, incorporating quantitative cognitive assessments and qualitative data from military athletes undergoing resilience training programs. Cognitive performance is evaluated through a battery of tests, including measures of memory, attention, decision-making, and reaction time. The participants, drawn from various branches of the military, are divided into experimental and control groups. The experimental group undergoes a comprehensive resilience training program, while the control group receives traditional physical training without a specific focus on resilience. The initial findings indicate a substantial improvement in cognitive performance among military athletes who have undergone resilience training. These improvements are particularly evident in domains such as attention and decision-making. The experimental group demonstrated enhanced situational awareness, quicker problem-solving abilities, and increased adaptability in high-stress scenarios. These results suggest that resilience training not only bolsters mental toughness but also positively impacts cognitive skills critical to military operations. In addition to quantitative assessments, qualitative data is collected through interviews and surveys to gain insights into the subjective experiences of military athletes. Preliminary analysis of these narratives reveals that participants in the resilience training program report higher levels of self-confidence, emotional regulation, and an improved ability to manage stress. These psychological attributes contribute to their enhanced cognitive performance and overall readiness. Moreover, this study explores the potential long-term benefits of resilience training. By tracking participants over an extended period, we aim to assess the durability of cognitive improvements and their effects on overall mission success. Early results suggest that resilience training may serve as a protective factor against the detrimental effects of prolonged exposure to stressors, potentially reducing the risk of burnout and psychological trauma among military athletes. This research has significant implications for military organizations seeking to optimize the performance and well-being of their personnel. The findings suggest that integrating resilience training into the training regimen of military athletes can lead to a more resilient and cognitively capable force. This, in turn, may enhance mission success, reduce the risk of injuries, and improve the overall effectiveness of military operations. In conclusion, this study provides compelling evidence that resilience training positively impacts the cognitive performance of military athletes. The preliminary results indicate improvements in attention, decision-making, and adaptability, as well as increased psychological resilience. As the study progresses and incorporates long-term follow-ups, it is expected to provide valuable insights into the enduring effects of resilience training on the cognitive readiness of military athletes, contributing to the ongoing efforts to optimize military personnel's physical and mental capabilities in the face of ever-evolving challenges.

Keywords: military athletes, cognitive performance, resilience training, cognitive enhancement program

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Authors: Sarah Niklas, Lynne Chester, Mark Diesendorf

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Geopolitical tensions, climate change and recent movements favouring a transformative shift in institutional power structures have influenced the economics of conventional energy supply for decades. This study takes a multi-dimensional approach to illustrate the potential of renewable energy (RE) technology to provide a pathway to a low-carbon economy driven by ecologically sustainable, independent and socially just energy. This comparative analysis identifies economic, political and social drivers that shaped the adoption of RE policy in two significantly different economies, Germany and Australia, with strong and weak commitments to RE respectively. Two complementary political-economy theories frame the document-based analysis. Régulation Theory, inspired by Marxist ideas and strongly influenced by contemporary economic problems, provides the background to explore the social relationships contributing the adoption of RE within the macro-economy. Varieties of Capitalism theory, a more recently developed micro-economic approach, examines the nature of state-firm relationships. Together these approaches provide a comprehensive lens of analysis. Germany’s energy policy transformed substantially over the second half of the last century. The development is characterised by the coordination of societal, environmental and industrial demands throughout the advancement of capitalist regimes. In the Fordist regime, mass production based on coal drove Germany’s astounding economic recovery during the post-war period. Economic depression and the instability of institutional arrangements necessitated the impulsive seeking of national security and energy independence. During the postwar Flexi-Fordist period, quality-based production, innovation and technology-based competition schemes, particularly with regard to political power structures in and across Europe, favoured the adoption of RE. Innovation, knowledge and education were institutionalized, leading to the legislation of environmental concerns. Lastly the establishment of government-industry-based coordinative programs supported the phase out of nuclear power and the increased adoption of RE during the last decade. Australia’s energy policy is shaped by the country’s richness in mineral resources. Energy policy largely served coal mining, historically and currently one of the most capital-intense industry. Assisted by the macro-economic dimensions of institutional arrangements, social and financial capital is orientated towards the export-led and strongly demand-oriented economy. Here energy policy serves the maintenance of capital accumulation in the mining sector and the emerging Asian economies. The adoption of supportive renewable energy policy would challenge the distinct role of the mining industry within the (neo)-liberal market economy. The state’s protective role of the mining sector has resulted in weak commitment to RE policy and investment uncertainty in the energy sector. Recent developments, driven by strong public support for RE, emphasize the sense of community in urban and rural areas and the emergence of a bottom-up approach to adopt renewables. Thus, political economy frameworks on both the macro-economic (Regulation Theory) and micro-economic (Varieties of Capitalism theory) scales can together explain the strong commitment to RE in Germany vis-à-vis the weak commitment in Australia.

Keywords: political economy, regulation theory, renewable energy, social relationships, energy transitions

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Authors: Łukasz Mazur, Kamil Domaradzki, Bartosz Kamecki, Justyna Ignaczak, Sebastian Molin, Aleksander Gil, Tomasz Brylewski

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The rising global power consumption necessitates the development of new energy storage solutions. Prospective technologies include solid oxide electrolyzer cells (SOECs), which convert surplus electrical energy into hydrogen. An electrolyzer cell consists of a porous anode, and cathode, and a dense electrolyte. Power output is increased by connecting cells into stacks using interconnects. Interconnects are currently made from high-chromium ferritic steels – for example, Crofer 22 APU – which exhibit high oxidation resistance and a thermal expansion coefficient that is similar to that of electrode materials. These materials have one disadvantage – their area-specific resistance (ASR) gradually increases due to the formation of a Cr₂O₃ scale on their surface as a result of oxidation. The chromia in the scale also reacts with the water vapor present in the reaction media, forming volatile chromium oxyhydroxides, which in turn react with electrode materials and cause their deterioration. The electrochemical efficiency of SOECs thus decreases. To mitigate this, the interconnect surface can be modified with protective-conducting coatings of spinel or other materials. The high prices of SOEC components -especially the Crofer 22 APU- have prevented their widespread adoption. More inexpensive counterparts, therefore, need to be found, and their properties need to be enhanced to make them viable. Candidates include the Nirosta 4016/1,4016 low-chromium ferritic steel with a chromium content of just 16.3 wt%. This steel's resistance to high-temperature oxidation was improved by depositing Gd₂O₃ nanoparticles on its surface via either dip coating or electrolysis. Modification with CeO₂ or Ce₀.₉Y₀.₁O₂ nanoparticles deposited by means of spray pyrolysis was also tested. These methods were selected because of their low cost and simplicity of application. The aim of this study was to investigate the oxidation kinetics of Nirosta 4016/1,4016 modified using the afore-mentioned methods and to subsequently measure the obtained samples' ASR. The samples were oxidized for 100 h in the air as well as air/H₂O and Ar/H₂/H₂O mixtures at 1073 K. Such conditions reflect those found in the anode and cathode operating space during real-life use of SOECs. Phase and chemical composition and the microstructure of oxidation products were determined using XRD and SEM-EDS. ASR was measured over the range of 623-1073 K using a four-point, two-probe DC technique. The results indicate that the applied nanoparticles improve the oxidation resistance and electrical properties of the studied layered systems. The properties of individual systems varied significantly depending on the applied reaction medium. Gd₂O₃ nanoparticles improved oxidation resistance to a greater degree than either CeO₂ or Ce₀.₉Y₀.₁O₂ nanoparticles. On the other hand, the cerium-containing nanoparticles improved electrical properties regardless of the reaction medium. The ASR values of all surface-modified steel samples were below the 0.1 Ω.cm² threshold set for interconnect materials, which was exceeded in the case of the unmodified reference sample. It can be concluded that the applied modifications increased the oxidation resistance of Nirosta 4016/1.4016 to a level that allows its use as SOEC interconnect material. Acknowledgments: Funding of Research project supported by program "Excellence initiative – research university" for the AGH University of Krakow" is gratefully acknowledged (TB).

Keywords: cerium oxide, ferritic stainless steel, gadolinium oxide, interconnect, SOEC

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Authors: Leo Byrne, Neil Watts

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In the complex and evolving landscape of global trade, maritime sanctions emerge as a critical tool wielded by the international community to curb illegal activities and alter the behavior of non-compliant states and entities. These sanctions, designed to restrict or prohibit trade by sea with sanctioned jurisdictions, entities, or individuals, face continuous challenges due to the sophisticated evasion tactics employed by countries like North Korea. As the Democratic People's Republic of Korea (DPRK) diverts significant resources to circumvent these measures, understanding the nuances of their methodologies becomes imperative for maintaining the integrity of global trade systems. The DPRK, one of the most sanctioned nations globally, has developed an intricate network to facilitate its trade in illicit goods, ensuring the flow of revenue from designated activities continues unabated. Given its geographic and economic conditions, North Korea predominantly relies on maritime routes, utilizing foreign ports to route its illicit trade. This reliance on the sea is exploited through various sophisticated methods, including the use of front companies, falsification of documentation, commingling of bulk cargos, and physical alterations to vessels. These tactics enable the DPRK to navigate through the gaps in regulatory frameworks and lax oversight, effectively undermining international sanctions regimes Maritime sanctions carry significant implications for global trade, imposing heightened risks in the maritime domain. The deceptive practices employed not only by the DPRK but also by other high-risk jurisdictions, necessitate a comprehensive understanding of UN targeted sanctions. For stakeholders in the maritime sector—including maritime authorities, vessel owners, shipping companies, flag registries, and financial institutions serving the shipping industry—awareness and compliance are paramount. Violations can lead to severe consequences, including reputational damage, sanctions, hefty fines, and even imprisonment. To mitigate risks associated with these deceptive practices, it is crucial for maritime sector stakeholders to employ rigorous due diligence and regulatory compliance screening measures. Effective sanctions compliance serves as a protective shield against legal, financial, and reputational risks, preventing exploitation by international bad actors. This requires not only a deep understanding of the sanctions landscape but also the capability to identify and manage risks through informed decision-making and proactive risk management practices. As the DPRK and other sanctioned entities continue to evolve their sanctions evasion tactics, the international community must enhance its collective efforts to demystify and counter these practices. By leveraging more stringent compliance measures, stakeholders can safeguard against the illicit use of the maritime domain, reinforcing the effectiveness of maritime sanctions as a tool for global security. This paper seeks to dissect North Korea's adaptive strategies in the face of maritime sanctions. By examining up-to-date, geographically, and temporally relevant case studies, it aims to shed light on the primary nodes through which Pyongyang evades sanctions and smuggles goods via third-party ports. The goal is to propose multi-level interaction strategies, ranging from governmental interventions to localized enforcement mechanisms, to counteract these evasion tactics.

Keywords: maritime, maritime sanctions, international sanctions, compliance, risk

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Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

Abstract:

Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

Procedia PDF Downloads 46

Authors: Andrew Gennett

Abstract:

Designing for fungal development means embracing the symbiotic relationship between the living system and built environment. The potential of mycelium post-colonization is explored for the fabrication of advanced pure mycelium products, going beyond the conventional methods of aggregating materials. Fruiting induction imparts desired material properties such as enhanced environmental resistance. Production approach allows for simultaneous generation of multiple products while scaling up raw materials supply suitable for architectural applications. The following work explores the integration of fungal environmental perception with computational design of built fruiting chambers. Polyporales, are classified by their porous reproductive tissues supported by a wood-like context tissue covered by a hard waterproofing coat of hydrobpobins. Persisting for years in the wild, these species represent material properties that would be highly desired in moving beyond flat sheets of arial mycelium as with leather or bacon applications. Understanding the inherent environmental perception of fungi has become the basis for working with and inducing desired hyphal differentiation. Working within the native signal interpretation of a mycelium mass during fruiting induction provides the means to apply textures and color to the final finishing coat. A delicate interplay between meeting human-centered goals while designing around natural processes of living systems represents a blend of art and science. Architecturally, physical simulations inform model design for simple modular fruiting chambers that change as fungal growth progresses, while biological life science principles describe the internal computations occurring within the fungal hyphae. First, a form filling phase of growth is controlled by growth chamber environment. Second, an initiation phase of growth forms the final exterior finishing texture. Hyphal densification induces cellular cascades, in turn producing the classical hardened cuticle, UV protective molecule production, as well, as waterproofing finish. Upon fruiting process completion, the fully colonized spent substrate holds considerable value and is not considered waste. Instead, it becomes a valuable resource in the next cycle of production scale-up. However, the acquisition of new substrate resources poses a critical question, particularly as these resources become increasingly scarce. Pursuing a regenerative design paradigm from the environmental perspective, the usage of “agricultural waste” for architectural materials would prove a continuation of the destructive practices established by the previous industrial regime. For these residues from fields and forests serve a vital ecological role protecting the soil surface in combating erosion while reducing evaporation and fostering a biologically diverse food web. Instead, urban centers have been identified as abundant sources of new substrate material. Diverting the waste from secondary locations such as food processing centers, papers mills, and recycling facilities not only reduces landfill burden but leverages the latent value of these waste steams as precious resources for mycelium cultivation. In conclusion, working with living systems through innovative built environments for fungal development, provides the needed gain of function and resilience of mycelium products. The next generation of sustainable fungal products will go beyond the current binding process, with a focus upon reducing landfill burden from urban centers. In final considerations, biophilic material builds to an ecologically regenerative recycling production cycle.

Keywords: regenerative agriculture, mycelium fabrication, growth chamber design, sustainable resource acquisition, fungal morphogenesis, soil fertility

Procedia PDF Downloads 35

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

Procedia PDF Downloads 44

Authors: Hosein Maghsoudi

Abstract:

Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

Procedia PDF Downloads 360

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

Procedia PDF Downloads 54